Method of treating mammals displaying severe neurological symptoms of advanced canine distemper virus infection using ndv-induced serum

ABSTRACT

This application discloses methods, compositions, and articles of manufacture for using NDV-induced serum to treat non-human mammals, including dogs, displaying severe neurological symptoms of advanced canine distemper virus (CDV) infection. An off-the-shelf chicken vaccine is injected into two or-more healthy mammals, of the same species as the sick animal, to provoke an immune response. After allowing several hours for the immune response to develop, blood is drawn from the healthy mammals and centrifuged to obtain serum. This “NDV-induced serum” can be injected into a mammal of the same species displaying severe neurological symptoms of advanced CDV infection on a prescribed schedule to bolster the sick animal&#39;s immune responses, preferably leading to clearance of the virus without the need for a spinal tap, which is the standard treatment for advanced CDV infection in mammals.

Canine distemper virus (CDV) causes a measles-like illness in dogs,weasels, raccoons, bobcats, larger cats, and other mammals. CDV spreadsquickly by coughing and sneezing, in addition to transmission throughurine, vomit, and/or feces. The domestic dog serves as the focus ofdiscussion of the invention, but the invention is not limited to thespecies listed.

Although a vaccine for CDV came into use more than 50 years ago, CDVruns rampant in many countries. In the United States, dog owners widelyadhere to vaccination guidelines and CDV outbreaks tend to occur whereunvaccinated dogs are in close quarters, such as in animal shelters. CDVtypically takes 1-3 weeks to incubate, with virus shedding in all bodilyexcretions beginning 7-10 days following infection. An infected dog maybe contagious for up to 3 months. Because treatment for viral illnessrequires isolation, supportive care (e.g., parenteral administration offluids for dehydrated animals), and stringent biosecurity measures, manyshelters in the United States opt to euthanize all dogs onsite whenconfronted with a suspected case of CDV.

CDV causes systemic infection in epithelial tissues throughout the body.Early on, viral replication takes place in the cells lining the mouthand nose, leading to the hallmark symptoms of cough and eye/nosedischarge, before spreading to the bloodstream, liver, digestive tract,and eventually the central nervous system (CNS). Fever accompaniesincreased virus production, as can anorexia, dehydration, and lethargy.Over 80% of puppies and 50% of adult dogs infected with CDV die. Yetdespite the substantial damage it inflicts, the single-stranded RNAvirus responsible for CDV cannot survive long outside a live host, givenits susceptibility to UV light, drying, heat, and routine disinfectants.

When the virus finds a host, the outcome of CDV infection typicallydepends on a range of factors, including the host's age, robustness ofits immune system, and virulence of the particular CDV strain. Animalswith weak immune systems often develop more extensive viral infections(and secondary bacterial infections like pneumonia), which often lead todeath. Animals that recover from the initial respiratory symptomstypically harbor the virus and will most likely develop severe CNSsymptoms associated with the advanced stage of distemper. And even withanimals having immune responses robust enough to stave off initialsymptoms of infection, CNS symptoms may eventually develop. Neurologicsymptoms can manifest 1-3 weeks after recovery from upper respiratorysymptoms. Telltale signs that the distemper virus has established itselfin the CNS include limb paralysis (paraparesis), seizures, jerky muscles(myoclonus), and loss of full control of movement (ataxia), among othersymptoms.

In addition to observing clinical manifestations of CDV infection,additional means of diagnosis include, but are not limited to, caninedistemper polymerase chain reaction (PCR) (whole blood, spinal fluid, orconjunctival scrape), spinal fluid analysis, canine distemper antibodyassays (spinal fluid, serum), spinal fluid analysis, NDV PCR (spinalfluid), and the like (Harkin & Wilkinson). PCR tests such as IDEXXReaIPCR™ can distinguish CDV infection from CDV vaccination in dogs.

In the wild, CDV causes illness in a variety of mammalian species,including canids (domestic dog, wolf, coyote, fox, jackal, dingo, andthe like), mustelids (weasels, badgers, otters, minks, martens,polecats, wolverines, and the like), procyonids (raccoons, coatis,olingos, olinguitos, ringtails, cacomistles, kinkajous, and the like),and large felids (bobcats, wildcats, ocelots, lynxes, cheetahs, servals,leopards, snow leopards, cougars, pumas, tigers, lions, and the like),and other species. As noted above, this description will primarily referto domestic dogs, but the reader should not infer any limitation as tothe species listed. The other most widely domesticated mammal, thedomestic cat, does not fall ill due to CDV, but instead can fall prey tofeline distemper virus.

TECHNICAL FIELD

The embodiments of the invention described and claimed here fall underthe field of veterinary biologics and treatment of viral disease inmammals.

BACKGROUND ART

The first description of canine distemper as an infectious disease indogs was published in 1905 and its viral origin was clearly demonstratedby 1926. By 1940, there was a patented process for preparation of caninedistemper vaccine (U.S. Pat. No. 2,202,435 A), and by 1965, a patentedmethod of using a measles vaccine to induce distemper resistance in dogs(U.S. Pat. No. 3,285,817 A).

By at least 1998, it was disclosed that CDV could be treated byadministration of antibodies parenterally using, e.g., Product R, apeptide-nucleic acid preparation (U.S. Pat. No. 5,807,840 A). U.S. Pat.No. 6,383,741 B2 disclosed treatment capable of relieving CDV symptomsby administering attenuated canine distemper or measles virus. See alsoU.S. Pat. Nos. 4,992,272 A and 5,000,951 A for vaccines using attenuatedCDV. Similarly, U.S. Pat. No. 3,836,648 A teaches a therapeutic CDVagent having a specific type of inactivated bacterium.

As for eliciting immune response in one animal to treat another, U.S.Pat. No. 8,052,971 B2 teaches immunizing a healthy mammal with anenteric disease antigen and subsequently harvesting antibodies to thatantigen from the plasma of the healthy mammal and, in turn, orallyadministering the antibody-rich plasma to another mammal suffering fromthe enteric disease. In a similar vein, U.S. Pat. No. 6,719,984 B1describes immunostimulation of a mammal with immune system components ina specific molecular weight range, which were obtained from the blood ofanother mammal.

With regard to Newcastle Disease Vaccine (NDV), it has been known sincethe 1970s that animals with early respiratory stage CDV infectionrespond well to injection of serum harvested from a healthy animal ofthe same species earlier injected with the NDV chicken vaccine. See,e.g., “NDV Serum Treatment for Dogs.” Protocols for preparing so-called“NDV-Induced Serum” appear to have been readily available on theinternet since at least 2009, e.g., “NDV-Induced Serum” available atwww.kindheartsinaction.com/archives/82.

Published compilations of anecdotal reports of veterinarians' use ofNDV-induced serum for treating early (that is, respiratory) CDVinfection, include one case where the serum was injected into the spinalfluid to treat symptoms of advanced CDV infection, i.e., CDV infectionwith severe neurological symptoms. Notably, however, this same reportstates that the so-called “NDV spinal tap” saves less than half of dogswith advanced CDV infection (see “Report on Effectiveness,” page 4, lastparagraph). Similarly, “Using the NDV Before Seizures” describesinjecting NDV into dogs sick with CDV to prevent seizures—rather thaninto healthy dogs for serum harvest first—but only where dog is olderthan 12 weeks and has not started having seizures.

Technical Problem

Spinal tap administration of NDV vaccine has been the standard treatmentfor dogs displaying severe neurological symptoms of advanced CDVinfection, such as frequent seizures. Spinal tap procedures, however,require advanced veterinary skill and operating facilities, and carryconcomitantly greater costs, as well as the risk of infecting the spinalfluid of the subject and causing serious complications such asmeningitis (Harkin & Wilkerson). Preparation and administration ofNDV-induced serum is widely known but has only been used for treatingearly respiratory symptoms of CDV. Until now, there has not been aneffective, low-cost method for treating advanced stages of CDV infectionin dogs displaying late neurological symptoms.

Accordingly, there exists a need in the art for compositions, articlesof manufacture, and methods for treating mammals, especially domesticdogs, exhibiting advanced stages of CDV infection. In addition, thereexists a need in the art for compositions, articles of manufacture, andmethods for treating these mammals without resorting to spinal tapprocedures.

SUMMARY OF INVENTION

This invention aids in resolving these needs in the art.

In one embodiment, this invention provides a method of treating a mammalhaving neurological symptoms of canine distemper virus (CDV) infection.The mammal is treated by administering two or more separate compositionsthat are not mixed, each comprising serum collected from a healthymember of the same species earlier injected with Newcastle DiseaseVaccine (NDV). The treated mammal survives and would test negative forCDV infection using widely available lab testing such as PCR. Examplesof mammals that can be treated according to the invention include acanid, a mustelid, a procyonid, or a felid that is larger than adomestic cat.

Examples of species of mammals that can be treated include a domesticdog, wolf, coyote, fox, jackal, dingo, other dog-like mammal, a weasel,badger, otter, mink, marten, polecat, wolverine, other weasel-likemammal, a raccoon, coati, olingo, olinguito, ringtail, cacomistle,kinkajou, other raccoon-like mammal, a bobcat, wildcat, ocelot, lynx,cheetah, serval, leopard, snow leopard, cougar, puma, tiger, lion, orother cat-like mammal that is larger than a domestic cat.

In another embodiment, this invention provides a method of treating adog with neurological symptoms of canine distemper virus (CDV)infection, which comprises administering to the dog two or more separatecompositions that are not mixed, each comprising serum collected from ahealthy dog earlier injected with Newcastle Disease Vaccine (NDV).Preferably, the dog is a domestic dog and treatment is carried outwithout spinal tap procedures. Examples of healthy dogs earlier injectedwith NDV that can be employed in the invention are dogs, 10-48 monthsold, of mixed breed, such as a black Labrador mix or border collie mix,weighing 40-120 pounds, without any autoimmune disorders, mange, mites,arthritis, or the like, and optionally unaltered, i.e., neither spayednor neutered.

This invention also provides an article of manufacture for treating amammal with neurological symptoms of CDV infection. The article ofmanufacture comprises two or more separate compositions that are notmixed, each comprising serum collected from a healthy member of the samespecies earlier injected with Newcastle Disease Vaccine (NDV), whereintreating the mammal with the compositions results in the mammalsurviving and becoming not infectious for canine distemper.

This invention provides straightforward, user-friendly ways to treatmammals, especially domestic dogs, showing severe neurological symptomsof advanced CDV infection. The compositions, articles of manufacture,and methods of the invention require less equipment than traditionalspinal tap treatment and consequently avoid higher costs and risks ofinfecting spinal fluid.

DETAILED DESCRIPTION

This invention provides compositions, articles of manufacture, andmethods for treating a mammal, preferably a domestic dog, that exhibitsneurological symptoms of canine distemper virus infection. As usedherein, the term canine distemper is used in its conventional sense asreferring to a contagious and serious disease caused by asingle-stranded virus designated canine morbillivirus.

CDV infections cause progressively more severe neurological symptomsover time:

-   -   Initial Stage—typified by “upper respiratory symptoms,” such as        persistent cough, high fever, red eyes, watery or green-colored        discharge from eyes and nose, lethargy, and often vomiting,        diarrhea, and loss of interest in food;    -   Intermediate Stage—typified by fairly mild “early neurological        symptoms,” such as occasional seizures, mild paralysis, mild        myoclonus; and    -   Advanced Stage—typified by more severe “late neurological        symptoms,” such as frequent seizures, fits, paralysis, and even        hysteria attacks.

The mammal treated for CDV infection and the healthy members of the samespecies earlier injected with the NDV can be selected from a canid, amustelid, a procyonid, or a felid that is larger than a domestic cat.The canid can be a domestic dog, wolf, coyote, fox, jackal, dingo, orother dog-like mammal. The mustelid can be a weasel, badger, otter,mink, marten, polecat, wolverine, or other weasel-like mammal. Theprocyonid can be a raccoon, coati, olingo, olinguito, ringtail,cacomistle, kinkajou, or other raccoon-like mammal. When the mammal is afelid, the felid can be a bobcat, wildcat, ocelot, lynx, cheetah,serval, leopard, snow leopard, cougar, puma, tiger, lion, or othercat-like mammal that is larger than a domestic cat.

Preferably, the mammal is a domestic dog and the healthy members of thesame species earlier injected with the NDV are domestic dogs. As usedherein, a domestic dog is a member of the genus Canis that has beendomesticated by man, also known as Canis (lupus) familiaris or, simply,a dog.

When the mammal being treated and the donor mammals are domestic dogs,healthy member of the same species would be healthy donor dogs. Suchdogs can be 10-48 months old, mixed breed, 40-120 lbs, preferablyunaltered, and healthy, without any autoimmune disorders, mange, mites,arthritis, or the like. In particular, two or more donor dogs should beused for each batch of serum, i.e., NDV-induced serum from two or morehealthy dogs will be used to treat one sick dog. The donor dogs arepreferably free of immune suppressants, such as corticosteroids and/orantihistamines, for at least 14 days before this procedure. ForNDV-induced serum to have potent effects, any mixed breed may be used,but black lab mixes and border collie mixes are preferable; pure breedsor individuals known to have immune deficiency problems are lesspreferable.

The reader should not infer that the embodiments of the inventiondisclosed here are limited to domestic dogs; for this discussion about ahealthy member of the same species, dogs are merely an example.

An effective amount of NDV-induced serum, or therapeutically effectivederivative(s) made from it, can be administered to an animal by mouth intablet or capsule form, by injection—intravenously (IV), parenterally,or subcutaneously—in liquid form, or by any pharmaceutically acceptableformulation having helpful characteristics such as enhanced taste,stability, convenience, solubility, and so on. These variousadministration forms may be produced by any methods well known in thepharmaceutical arts.

To facilitate treating a sick animal by mouth with NDV-induced serum, ortherapeutically effective derivative(s) made from it, an inert diluentcombined with an edible carrier can be employed, as well asencapsulation in gelatin or compression into tablets. Combination withexcipients can allow for tablets, capsules, suspensions, wafers,elixirs, semi-solids, granules, soft chews, chewable tablets, and soforth to produce stable dosage forms. These preparations should have atleast 0.1% NDV-induced serum, or therapeutically effective derivative(s)made from it, but this amount can range widely form to form, so long asa suitable dosage results. Forms that animals will readily consume ontheir own are favored.

Capsules, pills, tablets, etc., can contain: a binder like gelatin,microcrystalline cellulose, or natural gum; an excipient like lactose orstarch; a lubricant like magnesium stearate; a disintegrating agent likecorn starch or alginic acid; a glidant like colloidal silicon dioxide;or a flavoring agent like those found in animal feed, such as powdershaving meat, chicken, or sweet molasses flavors. Capsular forms mayfurther contain a carrier liquid like a fatty oil. The dosage units formcan also be modified by coating, e.g., enteric coating, as well as theaddition of dyes, colorings, and preservatives. In all instances, theresulting compositions should be non-toxic, pharmaceutically pure enoughfor use in animals, and suitable for delivery of a therapeuticallyeffective dosage.

For purposes of therapeutic administration by injection—whether IV,parenterally, or subcutaneously—the NDV-induced serum, ortherapeutically effective derivative(s) made from it, can be suspendedor dissolved in a suitable medium or injected as 100% serum obtainedfrom centrifuging blood from a donor animal. Forms requiringrefrigeration should be cooled appropriately and may be frozen, so longas the dosage unit retains therapeutic effectiveness. Solutions orsuspensions should have at least 0.1% NDV-induced serum, ortherapeutically effective derivative(s) made from it, but the percentagemay range widely, so long as a suitable dosage results.

With the present invention, the most preferable form for therapeuticadministration of NDV-induced serum, or therapeutically effectivederivative(s) made from it, is a composition comprising serum obtainedby centrifuging blood from a healthy donor as detailed below fortreating a mammal having neurological symptoms of CDV. The compositioncomprises serum collected from a healthy member of the same speciesearlier injected with Newcastle Disease Vaccine (NDV), also referred tohere as donor mammals, donor animals, donor dogs, or simply donors.

NDV is an infectious viral disease known to infect commercial andvillage chickens that can be controlled by the use of vaccines. Thereare different types of NDV vaccines, such as live vaccines and killedvaccines. In addition, there are different vaccine strains, such aslentogenic strains that are non-virulent and virulent strains that aremesogenic (intermediate virulence) or velogenic (highly virulent). Andthere are commercial versions of most of these strains. Specificallyexemplified here is the La Sota strain, B1 Type. But other vaccines typemay be considered.

Injecting NDV into a healthy donor dog will provoke an immune response,and NDV-induced serum is harvested from each donor dog's blood. Serumfrom each donor animal is kept separate from serum of each of the otherdonor animals for separate, sequential injections into an animalsickened by CDV infection, i.e., serum from different donor animals isnot combined. Further, after serving as a donor animal, the same animalshould never be used again for collection of NDV-induced serum, i.e.reinjected with NDV as detailed below.

Preparing and Collecting NDV-Induced Serum from Healthy Dogs

Preparation of NDV-induced serum generally follows publicly availableguidelines, such as those mentioned above. However, specific differencesexist and are detailed below.

Preferably, two or more donor dogs should be used for collecting eachbatch of serum, i.e., NDV-induced serum from two or more healthy dogswill be used to treat one sick dog without mixing or combining the serumor any composition comprising the serum, i.e., serum from differentdonor dogs should never be mixed. Preferably, the donor dogs should befree of immune suppressants, such as corticosteroids and/orantihistamines, for at least 14 days before this procedure.

Aliquots of Newcastle Disease Vaccine, for example, live, La Sotastrain, may be purchased commercially in lyophilized form (e.g., B1Type, La Sota Strain, Live Virus; Pfizer® List No. 1510855PFE: 10×5,000Doses). Add an appropriate diluent, such as Ringer's sodium lactatesolution (“RL”) or the like, to the NDV in the amount of 5-7 milliliters(“mis”) or most preferably about 6 mls. Immediately refrigerate theresulting solution. Anesthetize the donor dog and insert a catheter inits jugular vein; inject 5-7 mls or most preferably about 6 mls of NDVsolution via catheter (or equivalent amount of virus if diluteddifferently), and immediately flush IV with at least 5-7 mls or mostpreferably about 6 mls RL.

Because at least 2 donor animals are required, it is recommended thatthe timing of injections be staggered to allow sufficient time foranesthesia and pulling blood from multiple donor animals.

For harvest of NDV-induced serum in dogs, for example, anesthetize onedonor dog 9-13 hours post-NDV injection, or more preferably 10-12 hourspost-NDV injection, or most preferably just prior to the 11^(th) hourpost-NDV injection. Place the jugular catheter and start IV fluid. Drawblood under sterile conditions most preferably approximately 11 hourspost-NDV injection and inject into vials without any clotting agent(s).Allow blood to clot, and then centrifuge at a speed sufficient toisolate NDV-induced serum without rupturing red blood cells. This serumcan be used without further processing, i.e., it may be considered acomposition comprising serum suitable for injection without addition ofany further components. In the same vein, the serum may be furtherprocessed by any methods well known in the pharmaceutical arts toproduce any form for administration that remains therapeuticallyeffective, e.g., suspended or dissolved in a suitable medium asdiscussed above.

The amount of blood drawn should fall within generally acceptedguidelines (i.e., 1-2% of body weight, with IV fluid replacement fordraws higher than 1%). For example, a 1% draw from a 100-lb (45-kg) dogwould be 450 mls, with fluid replacement for a larger draw—not to exceed900 mls. Isolated NDV-induced serum may be stored in sterile containersunder refrigeration for up to 3 months, or longer if frozen.

Preparations for Treating CDV Infection Using NDV-Induced Serum

Initial Stage (Upper Respiratory Symptoms):

For a dog in the initial stage of CDV infection (upper respiratorysymptoms only), antibiotics should be started to address or ward off anysecondary bacterial infections, e.g., enrofloxacin (Baytril®) withclindamycin. The dog should be examined for infections and treated asneeded, e.g., deworming, eye antibiotics, etc. A pure protein diet withprobiotic addition(s) is recommended to foster healthy gut flora, e.g.,chicken and yogurt. Treatment with NDV-induced serum from healthy donordogs, or with two or more compositions that are not mixed and that eachcomprise serum from a healthy donor dog, should preferably commenceconcurrently.

Intermediate Stage (Early Neurological Symptoms):

For a dog displaying early neurological symptoms such as occasionalseizures, an anti-seizure medication like phenobarbital should beadministered, in addition to any antibiotics needed to address or wardoff any secondary bacterial infections, e.g., enrofloxacin (Baytril®)with clindamycin. The dog should be examined and treated as needed,e.g., deworming, eye antibiotics, IV fluids for dehydration, etc.Steroids are preferably avoided for dogs showing early neurologicalsymptoms. A pure protein diet with probiotic addition(s) is recommendedto foster healthy gut flora, e.g., chicken and yogurt. For dogs hesitantto eat, dextrose by IV is suggested.

Begin treating with NDV-induced serum right away, as described below;keep the dog in as low-stress an environment as possible, preferablywhere it is able to walk around freely rather than being crated.

Advanced Stage (Late Neurological Symptoms):

In the advanced stage of CDV infection, symptoms arise from the viralinfection as well as the dog's auto-immune response. For this reason,treatment of dogs showing late (i.e., severe) neurological symptomspreferably encompasses the treatment described above for theintermediate stage, and is augmented with steroid treatment (e.g.,dexamethasone) to suppress the auto-immune response. This steroidtreatment may go from 4-6 days depending on the animal's response. Suchsteroid treatment has the added benefit of ameliorating encephalitispain and inflammation often seen in dogs with advanced stage CDVinfection.

For advanced stage treatment, the first round of NDV-induced serumadministration consists of two or more injections of donor dogs'NDV-induced serum, with each injection spaced eight hours apart. Thedonor dogs' NDV-induced serum should be kept separate and administeredby intravenous (IV) injection one-at-a-time via IV port in the cephalicvein, i.e., first injection using NDV-induced serum from Dog A, secondfrom Dog B, and so forth. For the second round of treatment, the timebetween injections should be 10 hours. Fluids should be administered byIV as needed to address dehydration.

After treatment (depending on the stage of CDV infection reached), thedogs should test negative for the virus after 5-6 weeks using widelyavailable lab testing such as PCR.

Summary of Injection Schedule for Treating CDV Infection UsingNDV-Induced Serum

Treating Dogs with Only Upper Respiratory Symptoms (Initial StageDistemper)

For dogs with only upper respiratory symptoms, the first round oftreatment comprises injection of 4-6 mls or more preferably 5 mls ofNDV-induced serum drawn from each donor dog, with the injections spaced10 hours apart. Thus, 4-6 mls or more preferably 5 mls from Dog Afollowed 10 hours later with 4-6 mls or more preferably 5 mls from DogB, and so on. The second round of treatment uses NDV-induced serum fromthe same donor dogs, but injections are spaced 12 hours apart.

Treating Dogs with Early Neurological Symptoms (Intermediate StageDistemper)

For dogs exhibiting early neurological symptoms, follow the treatmentoutlined above for dogs that have only upper respiratory symptoms, butrepeat the treatment at least approximately 24 hours later. If symptomsreturn or worsen, the treatment may be repeated again after at leastapproximately another 24 hours.

Treating Dogs with Late (i.e., Severe) Neurological Symptoms (AdvancedStage Distemper)

For dogs exhibiting late neurological symptoms, more aggressivetreatment is recommended in the form of shortened intervals betweenNDV-induced serum administrations. In the first round of treatment, thetime between injections should be shortened to 8 hours; in the secondround, 10 hours.

EXAMPLES Example 1

Thirteen dogs sharing the following characteristics were treated for CDVinfection using NDV-induced serum as described here: diagnosis by labtesting such as PCR and observation of symptoms both, showed upperrespiratory infection and neurological symptoms at the beginning oftreatment, received vaccine within 6 weeks of becoming ill, but noearlier CDV vaccine. Following treatment for CDV infection showingneurological symptoms using NDV-induced serum as described here, eightof thirteen dogs survived—yielding a survival rate of 62%. Table 1summarizes treatment outcomes for these dogs and the dogs in the otherExamples below.

TABLE 1 Summary of treatment outcomes in 48 dogs described in Examples1-7. Symptoms of CDV infection Vaccine history Diagnosis NeurologicalVaccinated Treatment outcome Ex. # Lab Respiratory (intermed/ within 6weeks No prior Died w/ Survival (Dog Grp #) test Symptoms (early)advance) of illness vaccine Survived disease rate 1 x x x x x 8 5  62% 2x x x 13 0 100% 3 x x x x 5 0 100% 4 x x x x 6 2  75% 5 x x x x 1 4  20%6 x x x x 2 0 100% 7 x x x x x 2 0 100% 37 11  77%

Example 2

Thirteen dogs sharing the following characteristics were treated for CDVinfection using NDV-induced serum as described here: diagnosis byobservation of symptoms, but not lab testing, showed neurologicalsymptoms at the beginning of treatment, but not upper respiratorysymptoms, received vaccine within 6 weeks of becoming ill, but noearlier CDV vaccine. Following treatment for CDV infection showingneurological symptoms using NDV-induced serum as described here, allthirteen dogs survived—yielding a survival rate of 100%. See Table 1 fortreatment outcome summary.

Example 3

Five dogs sharing the following characteristics were treated for CDVinfection using NDV-induced serum as described here: diagnosis by labtesting such as PCR and observation of symptoms both, showedneurological symptoms at the beginning of treatment, but not upperrespiratory symptoms, received vaccine within 6 weeks of becoming ill,but no earlier CDV vaccine. Following treatment for CDV infectionshowing neurological symptoms using NDV-induced serum as described here,all five dogs survived—yielding a survival rate of 100%. See Table 1 fortreatment outcome summary.

Example 4

Eight dogs sharing the following characteristics were treated for CDVinfection using NDV-induced serum as described here: diagnosis byobservation of symptoms, but not lab testing, showed neurologicalsymptoms at the beginning of treatment as well as upper respiratorysymptoms, received vaccine within 6 weeks of becoming ill, but noearlier CDV vaccine. Following treatment for CDV infection showingneurological symptoms using NDV-induced serum as described here, six ofeight dogs survived—yielding a survival rate of 75%. See Table 1 fortreatment outcome summary.

Example 5

Five dogs sharing the following characteristics were treated for CDVinfection using NDV-induced serum as described here: diagnosis byobservation of symptoms, but not lab testing, showed neurologicalsymptoms at the beginning of treatment as well as upper respiratorysymptoms, had not ever gotten any CDV vaccine prior to treatment.Following treatment for CDV infection showing neurological symptomsusing NDV-induced serum as described here, one of five dogssurvived—yielding a survival rate of 20%. See Table 1 for treatmentoutcome summary.

Example 6

Two dogs sharing the following characteristics were treated for CDVinfection using NDV-induced serum as described here: diagnosis byobservation of symptoms and lab testing such as PCR, showed neurologicalsymptoms at the beginning of treatment but not upper respiratorysymptoms, had gotten CDV vaccine within 6 weeks of becoming ill but notearlier. Following treatment for CDV infection showing neurologicalsymptoms using NDV-induced serum as described here, both dogssurvived—yielding a survival rate of 100% for Example 6. See Table 1 fortreatment outcome summary.

Example 7

Two dogs sharing the following characteristics were treated for CDVinfection using NDV-induced serum as described here: diagnosis byobservation of symptoms, as well as lab testing such as PCR, showedneurological symptoms at the beginning of treatment as well as upperrespiratory symptoms, and had never gotten any CDV vaccine prior totreatment. Following treatment for CDV infection showing neurologicalsymptoms using NDV-induced serum as described here, both dogs survived.See Table 1 for treatment outcome summary.

Although the exact immunological mechanism remains unclear,administration of NDV-induced serum on a schedule, as disclosed here,bolsters the immune response of the sick dog. Until now, however,NDV-induced serum was thought not to be effective at treating dogsdisplaying late (i.e., severe) neurological symptoms of advanced stagedistemper. Instead, skilled artisans would expect the only possibletreatment to require a spinal tap. Further, a skilled artisan would haveexpected treatment following an NDV-induced serum protocol not to eithersave or effectively clear CDV from a dog exhibiting late neurologicalsymptoms, as the inventor describes here.

CITATION LIST Cited Patent Literature

-   U.S. Pat. No. 2,202,435 A-   U.S. Pat. No. 3,285,817 A-   U.S. Pat. No. 3,836,648 A-   U.S. Pat. No. 4,992,272 A-   U.S. Pat. No. 5,000,951 A-   U.S. Pat. No. 5,807,840 A-   U.S. Pat. No. 6,383,741 B2-   U.S. Pat. No. 6,719,984 B1-   U.S. Pat. No. 8,052,971 B2

Cited Non-Patent Literature

-   Bond E. Newcastle Disease Vaccine (NDV) treatment for canine    distemper. 2010-01-15. Available at www.edbond.com/NDV_packet.pdf    (last accessed 2018-07-25).-   Bond E. Report on the Effectiveness of NDV Treatments. 2016-02-13.    Available at http://www.kindheartsinaction.com/archives/1353 (last    accessed 2018-07-25).-   Bond E. Using the NDV Before Seizures. 2010-01-11. Available at    www.kindheartsinaction.com/archives/313 (last accessed 2018-07-25).-   Harkin K, Wilkerson M. Evaluation of the therapeutic efficacy and    changes in cytokines in cerebrospinal fluid and plasma in dogs with    canine distemper encephalitis treated with intrathecal live    Newcastle Disease Virus vaccine [Research Proposal]. 2014. Available    at www.maddiesfund.org (last accessed 2018-07-25).-   Sears A. NDV-induced Serum. 2011. Available at    www.kindheartsinaction.com/archives/82 (last accessed 2018-07-25).-   Vahlenkamp T. Canine Distemper and Other Canine Viral Infections, in    Textbook of Veterinary Internal Medicine. 2016. Pages 1006-9.

1. A method of treating a mammal with neurological symptoms of caninedistemper virus (CDV) infection, comprising: administering separately tothe mammal compositions from each of two or more separate donor dogs,the compositions being separate and not mixed prior to administration,each composition comprising serum collected from a healthy member of thesame species previously injected with Newcastle Disease Vaccine (NDV),wherein treating the mammal with neurological symptoms of CDV infectionwith the compositions results in the mammal surviving and testingnegative for CDV infection.
 2. The method of claim 1 wherein the mammalis a canid, a mustelid, a procyonid, or a felid that is larger than adomestic cat.
 3. The method of claim 2, wherein the mammal is a domesticdog, wolf, coyote, fox, jackal, dingo, or other dog-like mammal; or aweasel, badger, otter, mink, marten, polecat, wolverine, or otherweasel-like mammal; or a raccoon, coati, olingo, olinguito, ringtail,cacomistle, kinkajou, or other raccoon-like mammal; or a bobcat,wildcat, ocelot, lynx, cheetah, serval, leopard, snow leopard, cougar,puma, tiger, lion, or other cat-like mammal that is larger than adomestic cat.
 4. A method of treating a dog with neurological symptomsof canine distemper virus (CDV) infection, comprising: separatelyadministering to the dog compositions from each of two or more separatedonor dogs, the compositions being separate and not mixed prior toadministration, each composition comprising serum collected from ahealthy dog earlier injected with Newcastle Disease Vaccine (NDV). 5.The method of claim 4, wherein treating is carried out without anyspinal tap procedure.
 6. (canceled)
 7. The method of claim 5, whereineach healthy dog is 10-48 months old, of mixed breed, weighing 40-120pounds, without any autoimmune disorders, mange, mites, arthritis, orthe like, and optionally unaltered.
 8. The method of claim 7, whereineach healthy dog is selected from a black labrador mix and border colliemix.
 9. The method of claim 8, wherein each healthy dog has been free ofat least one of immune suppressants, corticosteroids, and antihistaminesfor at least 14 days before NDV injection.
 10. (canceled)
 11. An articleof manufacture for treating a mammal with neurological symptoms of CDVinfection, comprising: compositions from each of two or more separatedonor dogs, the compositions being separate and not mixed prior toadministration, and and each composition comprising serum collected froma healthy member of the same species earlier injected with NewcastleDisease Vaccine (NDV), wherein administering to the mammal withneurological symptoms of CDV infection the article of manufactureresults in the mammal surviving and testing negative for CDV infection.12. The article of manufacture of claim 11, wherein the mammal is adomestic dog, wolf, coyote, fox, jackal, dingo, other dog-like mammal, aweasel, badger, otter, mink, marten, polecat, wolverine, otherweasel-like mammal, a raccoon, coati, olingo, olinguito, ringtail,cacomistle, kinkajou, other raccoon-like mammal, a bobcat, wildcat,ocelot, lynx, cheetah, serval, leopard, snow leopard, cougar, puma,tiger, lion, or other cat-like mammal that is larger than a domesticcat.
 13. The article of manufacture of claim 12, wherein each healthymember of the same species is 10-48 months old, of mixed breed, weighing40-120 pounds, without any autoimmune disorders, mange, mites,arthritis, or the like, and optionally unaltered, and the treated mammalsurvives and would test negative for CDV infection.
 14. (canceled) 15.The article of manufacture of claim 13, wherein each healthy dog isselected from a black labrador mix and border collie mix.
 16. Thearticle of manufacture of claim 13, wherein each healthy dog has beenfree of at least one of immune suppressants, corticosteroids, andantihistamines for at least 14 days before NDV injection.
 17. (canceled)18. The method of claim 1, wherein each composition is administered byintravenous (IV) injection via an IV port in the cephalic vein.
 19. Themethod of claim 4, wherein each composition is administered byintravenous (IV) injection via an IV port in the cephalic vein.
 20. Thearticle of manufacture of claim 11, wherein each composition isadministered by intravenous (IV) injection via an IV port in thecephalic vein.
 21. The method of claim 1, wherein the mammal is furthertreated with a steroid treatment.
 22. The method of claim 4, wherein themammal is further treated with a steroid treatment.
 23. The method ofclaim 1, wherein the mammal is injected with the compositions in atleast two rounds of treatment, the first round of treatment spaced eighthours apart from the second round of treatment.
 24. The method of claim4, wherein the mammal is injected with the compositions in at least tworounds of treatment, the first round of treatment spaced eight hoursapart from the second round of treatment.
 25. The method of claim 1,wherein the healthy mammal is injected with Newcastle Disease Vaccine(NDV) eleven hours before the composition comprising serum is collected.26. The method of claim 4 wherein the healthy mammal is injected withNewcastle Disease Vaccine (NDV) eleven hours before the compositioncomprising serum is collected.